Kelonia Therapeutics has shared the largest slice of data yet for its in vivo CAR-T, helping to justify the $3.2 billion price tag that Eli Lilly recently paid to buy the Boston biotech.
All 18 patients with relapsed or refractory multiple myeloma who have so far been treated with Kelonia’s KLN-1010 had no cancer in their bone marrow one month later, as determined by a test for minimal residual disease (MRD). All patients who are able to be assessed six months after treatment still had no cancer, and the patient with the longest follow-up—beyond 10 months—also remained MRD negative.
KLN-1010 is designed to deliver a gene to T cells within the body to arm them with the power to hunt down and kill cancer cells that express BCMA, a common protein on the surface of myeloma cells.
The updated data, which Kelonia presented Sunday at the American Society of Clinical Oncology annual meeting in Chicago, includes 14 new patients in addition to the four that the biotech grabbed headlines with at December’s American Society of Hematology conference.
Those initial four patients were “a peek behind the curtain” of in vivo CAR-T’s potential, Kelonia founder and CEO Kevin Friedman, Ph.D., told Fierce during an interview on the conference sidelines. Now, the biotech is quickly pulling back the curtain to find the data “still hold to be quite impressive.”
Lilly's oncology and business development leader, Jake Van Naarden, suggested that Friedman is underselling his company’s data.
“The data are remarkable,” Van Naarden told Fierce in a joint interview with Friedman. These patients are the sickest of the sick, and yet with no preconditioning, an off-the-shelf therapeutic delivered a 100% response rate and full MRD negativity so far, Van Naarden pointed out. “That is nutty.”
In addition to eradicating cancer, Friedman added, “the safety profile is exquisite for our medicine.” There were no reactions related to the infusion of KLN-1010, he said, and beyond that, the side effects were typical of traditional CAR-T approaches.
That includes 16 of the 18 patients experiencing cytokine release syndrome, Kelonia said in a May 31 release, with all cases classified as grade 1 or 2. There were also two cases of immune effector cell-associated neurotoxicity syndrome.
The safety profile makes it “highly feasible” that KLN-1010 can be moved into earlier lines of therapy, Friedman added.
While the first four patients Kelonia tested were in Australia, the trial has now expanded to the U.S. and enrollment is ongoing to find the right dose for later development. Though the acquisition has yet to close, Van Naarden is spending his time at ASCO holding meetings with myeloma experts to figure out the best possible path for phase 3 trials of Kelonia's therapy.
“Our goal would be to use the phase 1 study to define a dose and move directly into a suite of randomized phase 3 trials to generate definitive evidence,” Van Naarden explained. “We already have a bunch of those studies roughly sketched out.”
Beyond KLN-1010, Lilly has big plans for the rest of Kelonia’s platform. The lentiviral-based approach the biotech uses is “cassette-like,” Van Naarden said, and could be repurposed for a variety of cancers. A lymphoma candidate is already in the works, and the Lilly leader said solid tumors may be in the mix as well.
Lilly bought Kelonia and fellow in vivo biotech Orna Therapeutics, which uses a lipid nanoparticle-mRNA approach, this year after deciding the pharma needed a seat at the cell therapy game and finding that in vivo was more appealing than either established patient-derived CAR-Ts or work-in-progress donor-derived methods.
“We just felt like the ex vivo cell therapy thing was not a scaled pharmaceutical product,” Van Naarden told Fierce. After canvassing allogeneic, donor-derived methods as well as in vivo options, Lilly ultimately settled on the latter.
“It became clearer to us that—oh wow—in vivo might actually just leapfrog allo entirely,” he said.